Beta-amyloid Regulation of Presynaptic Transmission

Baylor College Of Medicine, Houston TX

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): This proposal aims to determine a novel role for Alzheimer's Disease (AD) beta-amyloid peptide in nicotinic acetylcholine receptor (nAChR)-induced regulation of synapsins, molecules that regulate the number of vesicles available for neurotransmitter release. Beta-amyloid binds to various nAChRs; however, whether these interactions affect presynaptic transmission remains unknown. My preliminary data shows that a nAChR agonist and/or the beta-amyloid alters phosphorylation of synapsins in acute mouse hippocampal slices. The experiments in this proposal will test the hypothesis that beta-amyloid couples to synapsin phosphorylation, thereby, modulating synaptic transmission via nAChRs at presynaptic terminals. To test this hypothesis, acute hippocampal slices from wild-type, nAChR subunit specific null mice, or transgenic mice with increased beta-amyloid will be assayed for changes in synapsin phosphorylation using western blotting. Presynaptic transmission will be evaluated using extracellular and whole-cell patch clamp recordings. The relevance of this project is that beta-amyloid regulation of neurotransmitter release via nAChRs could be one potential mechanism for the memory loss observed in AD patients. [unreadable] [unreadable] [unreadable]